Objectives The main objective of this work is to define the role of gd T lymphocytes in SIV/HIV infections ABSTRACT:Recent reports of the increase in peripheral blood gd T cells in the HIV+ patients prompted us to examine the gd T cell system in rhesus monkeys (Macaca mulatta) and the responses of these cells to SIV infection. Our results reveal differences in the gd T cell subset composition and their expression of CD8 in the peripheral blood of monkeys and humans. The outgrowth of simian gd T cells in response to Daudi cells is similar to that in humans, but the exposure to IL-2 stimulates preferentially the simian Vd1 subset instead of the Vg9/Vd2 subset as seen in humans. Upon SIV infection of the monkeys, we observed a transient increase of the percentage of total gd T cell and the Vg9 subset. gd T cells from infected animals also express more activation markers such as CD69, CD44 and the memory marker CD45RO. However, they respond to a lesser degree to Daudi or IL-2 stimulation in the outgrowth experiments compared to uninfected animals although the subset composition of total gd T cells is similar in infected and uninfected animals. The results clearly indicate that the gd T cells in rhesus monkeys are influenced by the SIV infection. The detailed analysis of the gd T cell response to SIV infection can serve as a model for understanding human gd T cell responses to human immunodeficiency virus (HIV) infections. Moreover, we have found that the constitutive recognition functions of the human Vg9/Vd2 T cell subset are severely altered in HIV+ individuals and we have initiated a detailed analysis of this previously unrecognized immunological defect associated with HIV infection. Keywords SIV, HIV, gd T cells